This is a K24 application for Talat Alp Ikizler, M.D. The candidate is faculty at Vanderbilt University Medical Center (VUMC), Division of Nephrology in the "Physician-Scientist" track with 80 % effort commitment to research. The candidate has focused his research efforts on the elucidation of multiple aspects of nutrition and metabolism in renal failure patients. At the time of this application, the candidate is the principal investigator of 3 federally and 2 non-federally funded grant awards and published 31 manuscripts and 6 book chapters. He is involved in mentoring of 5 past trainees and 3 current trainees. The immediate and long-term objectives of this grant application are to provide protected time for the applicant to focus on research and mentoring activities, specifically facilitate the independence of the current trainees and recruit beginning investigators interested in a rigorous approach to clinical investigation. In addition, the candidate will take a leadership position in clinical research enterprise at the Division of Nephrology. VUMC provides excellent resources for clinical research and mentoring, including the Nephrology Training Grant, Master of Science in Clinical Investigation and Master of Public Health programs (2 current and 1 future trainee enrolled in these programs), General Clinical Research Center and Clinical Nutrition Research Unit. In this proposal, we will investigate three promising approaches to improve the nutritional status of chronic hemodialysis (CHD) patients. First, we will examine the nutritional effects of chronic inflammation on protein and energy metabolism in hemodialysis patients and test the potential beneficial effects of an anti-inflammatory agent on these parameters. Second, we will examine the comparative effectiveness of two nutritional supplementation regimens on protein and energy metabolism in malnourished patients. These protocols will incorporate detailed protein and energy balance studies utilizing stable isotope infusion techniques. In a third study, we will test the hypothesis that recombinant human growth hormone interacts with nutritional supplementation to improve nutritional parameters in 150 CHD patients with overt signs of malnutrition using a prospective, randomized, placebo-controlled study clinical trial.